HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 288/4/F840    most recent 00240.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Zhang, M.-Z. Articles by Harris, R. C. Search for Related Content PubMed PubMed Citation Articles by Zhang, M.-Z. Articles by Harris, R. C.

Cross talk between the intrarenal dopaminergic and cyclooxygenase-2 systems

George O'Brien Center for Kidney and Urologic Diseases, and ¹Departments of Medicine and ²Cell and Developmental Biology, Vanderbilt University School of Medicine and Department of Veterans Affairs Medical Center, Nashville, Tennessee

Submitted 28 June 2004 ; accepted in final form 9 December 2004

In mammalian kidney, dopamine produced in the proximal tubule (PT) acts as an autocrine/paracrine natriuretic hormone that inhibits salt and fluid reabsorption in the PT. In high-salt-treated animals, PT dopamine activity increases and inhibits reabsorption, leading to increased salt and fluid delivery to the macula densa (MD) and subsequent natriuresis and diuresis. Regulated cyclooxygenase-2 (COX-2) in the MD represents another intrinsic system mediating renal salt and water homeostasis. Renal cortical COX-2 is inversely related to salt intake, and decreased extracellular NaCl stimulates COX-2 expression in cultured MD/cortical thick ascending limb cells. The current study investigated interactions between renal dopamine and cortical COX-2 systems. In rats fed a control diet, the dopamine precursor L-dihydroxyphenylalanine (L-DOPA) or the DA1 receptor agonist SKF-81297 suppressed cortical COX-2 expression. High salt suppressed cortical COX-2 expression, which was attenuated by inhibition of dopamine production with benserazide or the DA1 receptor antagonist, SCH-23390. In contrast, L-DOPA or the dopamine-metabolizing enzyme inhibitor entacapone suppressed low-salt-induced cortical COX-2 expression. Inhibition of PT reabsorption with the carbonic anhydrase inhibitor acetazolamide suppressed cortical COX-2 expression. In contrast, treatment with distally acting diuretics led to elevation of cortical COX-2. These results indicate that dopamine modulates renal cortical COX-2 expression by modifying PT reabsorption.

prostaglandin synthase G₂/H₂; cortex; proximal tubule reabsorption

This article has been cited by other articles:

				B. Yao, R. C. Harris, and M.-Z. Zhang Intrarenal Dopamine Attenuates Deoxycorticosterone Acetate/High Salt-Induced Blood Pressure Elevation in Part Through Activation of a Medullary Cyclooxygenase 2 Pathway Hypertension, November 1, 2009; 54(5): 1077 - 1083. [Abstract] [Full Text] [PDF]

				M.-Z. Zhang, B. Yao, X. Fang, S. Wang, J. P. Smith, and R. C. Harris Intrarenal Dopaminergic System Regulates Renin Expression Hypertension, March 1, 2009; 53(3): 564 - 570. [Abstract] [Full Text] [PDF]

				B. Yao, J. Xu, Z. Qi, R. C. Harris, and M.-Z. Zhang Role of renal cortical cyclooxygenase-2 expression in hyperfiltration in rats with high-protein intake Am J Physiol Renal Physiol, August 1, 2006; 291(2): F368 - F374. [Abstract] [Full Text] [PDF]